tbuckley/cabot-search huggingface dataset:
Sulfonium‐Cross‐Linked Hyaluronic Acid‐Based Self‐Healing Hydrogel: Stimuli‐Responsive Drug Carrier with Inherent Antibacterial Activity to Counteract Antibiotic‐Resistant Bacteria
Authors: Anjali Patel, Sanghamitra Goswami, Gunanka Hazarika, Senthilkumar Sivaprakasam, Surajit Bhattacharjee, Debasis Manna
Journal: Advanced Healthcare Materials (2023)

Abstract Augmentation of the activity of Food and Drug Administration‐approved antibiotics by an adjuvant or antibiotic carrier is considered one of the promising strategies to fight against antibiotic‐resistant bacteria. This study reports the development of sulfonium‐cross‐linked hyaluronic acid (HA)‐based polymer (HA‐SS‐HA) as an inherent antimicrobial agent and antibiotic carrier. The HA‐SS‐HA polymer offers the potential for encapsulating various classes of antibiotics and accomplishing a stimuli‐responsive release profile in the presence of hyaluronidase produced by bacterial cells within their extracellular environment. Systematic antibacterial studies reveal that the HA‐SS‐HA‐encapsulated antibiotics (vancomycin, amoxicillin, and tetracycline) restore its activity against the antibiotic‐resistant bacterial cells methicillin‐resistant Staphylococcus aureus (MRSA) and vancomycin‐resistant Enterococci (VRE), and Pseudomonas aeruginosa . The HA‐SS‐HA gel shows robust efficacy in eradicating the mature biofilm of Staphylococcus aureus ( S. aureus ). The membrane‐disrupting activity reveals that HA‐SS‐HA can also counteract the antibiotic resistance mechanism of the bacterial cells. The in vivo studies reveal excellent wound‐healing activity of HA‐SS‐HA in albino laboratory‐bred (BALB/c) mice. The outcome of additional antibacterial studies reveals that antibiotics‐encapsulated HA‐SS‐HA hydrogel can effectively combat Gram‐negative, Gram‐positive, and antibiotic‐resistant bacterial strains. Therefore, revitalizing the activity of commercial antibiotics by HA‐SS‐HA can be considered a valuable and economically effective strategy to fight against antibiotic‐resistant bacteria.
A New Wave of PI3Kα Inhibitors
Authors: Alison L. Kearney, Neil Vasan
Journal: Cancer Discovery (2023)

Summary: This is the first peer-reviewed report of an allosteric, mutant-selective PI3Kα inhibitor, STX-478, that reduces PIK3CA-mutant tumor growth in mice. However, in contrast to the FDA-approved PI3Kα isoform–selective inhibitor alpelisib, STX-478 does not induce hyperglycemia or other metabolic dysfunctions. See related article by Buckbinder et al., p. 2432 (7).
The Promise and Limitations of Neoadjuvant Immune-Checkpoint Blockade in Resectable Non–Small Cell Lung Cancer
Authors: Alissa J. Cooper, Helena A. Yu
Journal: Cancer Discovery (2023)

Summary: The landscape of neoadjuvant immune-checkpoint blockade for resectable non–small cell lung cancer has become an exciting area of clinical and translational exploration. Cascone and colleagues present a platform study of one cycle of novel immunomodulatory agents prior to surgical resection, offering a unique opportunity to perform translational biomarker studies, though many questions remain regarding the ultimate application to a broader patient population. See related article by Cascone et al., p. 2394 (1).
Association of Somatic <scp><i>TET2</i></scp> Mutations With Giant Cell Arteritis
Authors: Michelle L. Robinette, Lachelle D. Weeks, Ryan J. Kramer, Mridul Agrawal, Christopher J. Gibson, Zhi Yu, Aswin Sekar, Arnav Mehta, Abhishek Niroula, Jared T. Brown, Gregory C. McDermott, Edith R. Reshef, Jonathan E. Lu, Victor D. Liou, Carolina A. Chiou, Pradeep Natarajan, Suzanne K. Freitag, Deepak A. Rao, Benjamin L. Ebert
Journal: Arthritis & Rheumatology (2023)

Giant cell arteritis (GCA) is an age-related vasculitis. Prior studies have identified an association between GCA and hematologic malignancies (HMs). How the presence of somatic mutations that drive the development of HMs, or clonal hematopoiesis (CH), may influence clinical outcomes in GCA is not well understood.
Incorrect Author Affiliation
Journal: JAMA (2023)

Stephen P. Juraschek, MD, PhD; Jiun-Ruey Hu, MD, MPH; Jennifer L. Cluett, MD; Anthony M. Ishak, PharmD; Carol Mita, MLIS; Lewis A. Lipsitz, MD; Lawrence J. Appel, MD, MPH; Nigel S. Beckett, MB, ChB; Ruth L. Coleman, MSc; William C. Cushman, MD; Barry R. Davis, MD, PhD; Greg Grandits, MS; Rury R. Holman, MB, ChB; Edgar R. Miller 3rd, MD, PhD; Ruth Peters, PhD, MSc; Jan A. Staessen, MD, PhD; Addison A. Taylor, MD, PhD; Lutgarde Thijs, MSc; Jackson T. Wright Jr, MD, PhD; Kenneth J. Mukamal, MD, MPH, MA
Mitigating the Negative Mental Health Impact of Racism on Black Adolescents—A Preventive Perspective
Authors: Kevin M. Simon
Journal: JAMA Network Open (2023)

Steven M. Kogan, PhD; Elizabeth Kwon, PhD; Gene H. Brody, PhD; Rabeeh Azarmehr, MA; Ava J. Reck, MS; Tracy Anderson, PhD; Megan Sperr, MPA
Clonal Relationship and Mutation Analysis in Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia Associated With Diffuse Large B-cell Lymphoma
Authors: Madeleine R. Berendsen, Diede A.G. van Bladel, Eva Hesius, Cristina Berganza Irusquieta, Jos Rijntjes, Annemiek B. van Spriel, Ellen van der Spek, Johannes F.M. Pruijt, Leonie I. Kroeze, Konnie M. Hebeda, Sandra Croockewit, Wendy B.C. Stevens, J Han J.M. van Krieken, Patricia J.T.A. Groenen, Michiel van den Brand, Blanca Scheijen
Journal: HemaSphere (2023)

Patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) occasionally develop diffuse large B-cell lymphoma (DLBCL). This mostly results from LPL/WM transformation, although clonally unrelated DLBCL can also arise. LPL/WM is characterized by activating MYD88L265P (>95%) and CXCR4 mutations (~30%), but the genetic drivers of transformation remain to be identified. Here, in thirteen LPL/WM patients who developed DLBCL, the clonal relationship of LPL and DLBCL together with mutations contributing to transformation were investigated. In 2 LPL/WM patients (15%), high-throughput sequencing of immunoglobulin gene rearrangements showed evidence of >1 clonal B-cell population in LPL tissue biopsies. In the majority of LPL/WM patients, DLBCL presentations were clonally related to the dominant clone in LPL, providing evidence of transformation. However, in 3 patients (23%), DLBCL was clonally unrelated to the major malignant B-cell clone in LPL, of which 2 patients developed de novo DLBCL. In this study cohort, LPL displayed MYD88L265P mutation in 8 out of eleven patients analyzed (73%), while CXCR4 mutations were observed in 6 cases (55%). MYD88WT LPL biopsies present in 3 patients (27%) were characterized by CD79B and TNFAIP3 mutations. Upon transformation, DLBCL acquired novel mutations targeting BTG1, BTG2, CD79B, CARD11, TP53, and PIM1. Together, we demonstrate variable clonal B-cell dynamics in LPL/WM patients developing DLBCL, and the occurrence of clonally unrelated DLBCL in about one-quarter of LPL/WM patients. Moreover, we identified commonly mutated genes upon DLBCL transformation, which together with preserved mutations already present in LPL characterize the mutational landscape of DLBCL occurrences in LPL/WM patients.
Cooperative Armoring of CAR and TCR T Cells by T Cell–Restricted IL15 and IL21 Universally Enhances Solid Tumor Efficacy
Authors: Rosa Nguyen, Ekaterina Doubrovina, Charlotte M. Mousset, Benjamin Y. Jin, Reona Okada, Xiyuan Zhang, Arina Clavel, Jeyshka M. Reyes-Gonzalez, Vadim Dyomin, Louis Diaz, Ling Zhang, Shahroze Abbas, Ming Sun, Chao-Ming Hsieh, Mitchell Ho, Jack F. Shern, James L. Gulley, Christian S. Hinrichs
Journal: Clinical Cancer Research (2023)

Chimeric antigen receptor (CAR) and T-cell receptor (TCR) T-cell therapies are effective in a subset of patients with solid tumors, but new approaches are needed to universally improve patient outcomes. Here, we developed a technology to leverage the cooperative effects of IL15 and IL21, two common cytokine-receptor gamma chain family members with distinct, pleiotropic effects on T cells and other lymphocytes, to enhance the efficacy of adoptive T cells.
Xenobiotic Exposure and Migraine-Associated Signaling: A Multimethod Experimental Study Exploring Cellular Assays in Combination with <i>Ex Vivo</i> and <i>In Vivo</i> Mouse Models
Authors: Rikke H. Rasmussen, Sarah L. Christensen, Kirstine Calloe, Brian Skriver Nielsen, Anders Rehfeld, Thomas E. Taylor-Clark, Kristian A. Haanes, Olivier Taboureau, Karine Audouze, Dan A. Klaerke, Jes Olesen, David M. Kristensen
Journal: Environmental Health Perspectives (2023)

Mechanisms for how environmental chemicals might influence pain has received little attention. Epidemiological studies suggest that environmental factors such as pollutants might play a role in migraine prevalence. Potential targets for pollutants are the transient receptor potential (TRP) channels ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1), which on activation release pain-inducing neuropeptide calcitonin gene-related peptide (CGRP).In this study, we aimed to examine the hypothesis that environmental pollutants via TRP channel signaling and subsequent CGRP release trigger migraine signaling and pain.A calcium imaging-based screen of environmental chemicals was used to investigate activation of migraine pain-associated TRP channels TRPA1 and TRPV1. Based on this screen, whole-cell patch clamp and in silico docking were performed for the pesticide pentachlorophenol (PCP) as proof of concept. Subsequently, PCP-mediated release of CGRP and vasodilatory responses of cerebral arteries were investigated. Finally, we tested whether PCP could induce a TRPA1-dependent induction of cutaneous hypersensitivity in vivo in mice as a model of migraine-like pain.A total of 16 out of the 52 screened environmental chemicals activated TRPA1 at 10 or 100μM. None of the investigated compounds activated TRPV1. Using PCP as a model of chemical interaction with TRPA1, in silico molecular modeling suggested that PCP is stabilized in a lipid-binding pocket of TRPA1 in comparison with TRPV1. In vitro, ex vivo, and in vivo experiments showed that PCP induced calcium influx in neurons and resulted in a TRPA1-dependent CGRP release from the brainstem and dilation of cerebral arteries. In a mouse model of migraine-like pain, PCP induced a TRPA1-dependent increased pain response (Ntotal=144).Here we show that multiple environmental pollutants interact with the TRPA1-CGRP migraine pain pathway. The data provide valuable insights into how environmental chemicals can interact with neurobiology and provide a potential mechanism for putative increases in migraine prevalence over the last decades. https://doi.org/10.1289/EHP12413.
Audit Finds US National Stockpile “Was Not Equipped” for the Pandemic
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Error in Byline
Journal: JAMA Network Open (2023)

Kelli M. Rasmussen, MS; Vikas Patil, MS; Chunyang Li, PhD; Christina Yong, MA; Sreevalsa Appukkuttan, MBBS, MPH; Jamie Partridge Grossman, PhD, MBA; Jay Jhaveri, MD, MPH; Ahmad S. Halwani, MD
Prognostic Significance of Incipient Ulceration in Primary Cutaneous Melanoma
Authors: Elizabeth C. Paver, Tasnia Ahmed, Hazel Burke, Robyn P. M. Saw, Jonathan R. Stretch, Andrew J. Spillane, Kerwin F. Shannon, Ismael A. Vergara, David E. Elder, Serigne N. Lo, John F. Thompson, Richard A. Scolyer
Journal: JAMA Dermatology (2023)

Ulceration represents a key feature in cutaneous melanoma, contributing to staging according to the current American Joint Committee on Cancer (AJCC) system. However, cases with incipient ulceration do not quite fulfill the AJCC definition of ulceration and are consequently classified as nonulcerated, presenting interpretive difficulty for pathologists. The prognostic implication of incipient ulceration is uncertain.
Molecular Mechanism of Fasting-Mimicking Diet in Inhibiting Colorectal Cancer Progression: Implications for Immune Therapy and Metabolic Regulation
Authors: Clancy O. Bush, Rachel J. Perry
Journal: Cancer Research (2023)

Abstract Recently, fasting-mimicking diet and caloric restriction have been shown to improve antitumor immunity. In this issue of Cancer Research, Zhong and colleagues provide insights into the molecular mechanism of fasting-mimicking diet–mediated metabolic reprogramming in colorectal cancer progression. The authors performed comprehensive mechanistic experiments in mouse models to show that fasting-mimicking diet prevents colorectal cancer progression by lowering intratumoral IgA+ B cells by accelerating fatty acid oxidation to inhibit B-cell IgA class switching. In addition, they found that fatty acid oxidation–dependent acetylation prevents IgA class switching and that IgA+ B cells interfere with the anticancer effects of fasting-mimicking diet in colorectal cancer. Overall, their study establishes that fasting-mimicking diet has the potential to activate anticancer immunity and to induce tumor regression in colorectal cancer. See related article by Zhong et al., p. 3529
Cardiovascular and Venous Thromboembolic Risk With JAK Inhibitors in Immune-Mediated Inflammatory Skin Diseases
Authors: Jenne P. Ingrassia, Muhammad Haisum Maqsood, Joel M. Gelfand, Brittany N. Weber, Sripal Bangalore, Kristen I. Lo Sicco, Michael S. Garshick
Journal: JAMA Dermatology (2023)

Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and vitiligo, but there is a current US Food and Drug Administration (FDA) boxed warning label for oral and topical JAK inhibitors regarding increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections, malignant neoplasm, and death. However, this boxed warning was precipitated by results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, which only included patients with rheumatoid arthritis, and the same association may not be observed in dermatologic conditions.
Family-Centered Prevention to Reduce Discrimination-Related Depressive Symptoms Among Black Adolescents
Authors: Steven M. Kogan, Elizabeth Kwon, Gene H. Brody, Rabeeh Azarmehr, Ava J. Reck, Tracy Anderson, Megan Sperr
Journal: JAMA Network Open (2023)

Importance Racial discrimination undermines the mental health of Black adolescents. Preventive interventions that can attenuate the effects of exposure to racial discrimination are needed. Objective To investigate whether participation in the Strong African American Families (SAAF) program moderates Black adolescents’ depressive symptoms associated with experience of racial discrimination. Design, Setting, and Participants This secondary analysis used data from a community-based randomized clinical trial of SAAF (SAAF vs no treatment control). Participants were followed up at 10, 22, and 34 months after the baseline assessment. Assessment staff were blind to participant condition. Participants in this trial lived in 7 rural counties in Georgia. SAAF was delivered at local community centers. Eligible families had a child aged 11 to 12 years who self-identified as African American or Black. The joint influence of random assignment to SAAF and exposure to racial discrimination was investigated. Data were analyzed from September 2022 to March 2023. Intervention SAAF is a 7-session (14 hours) family skills training intervention that occurs over 7 weeks. Small groups of caregivers and their adolescents participate in a structured curriculum targeting effective parenting behavior, adolescent self-regulation, and Black pride. Main Outcomes and Measures The main outcome was adolescent-reported depressive symptoms, assessed at 34 months via the 20-item Center for Epidemiologic Studies Depression Scale for Children. Results Of 825 families screened randomly from public school lists, 472 adolescents (mean [SD] age, 11.6 years; 240 [50.8%] female) were enrolled and randomized to SAAF (252 participants) or a no treatment control (220 participants). Exposure to racial discrimination at age 13 years was associated with increased depressive symptoms at age 14 years (β = 0.23; 95% CI, 0.13 to 0.34; P &amp;amp;lt; .001). Interaction analyses indicated that the experimental condition significantly moderated the association of racial discrimination with depressive symptoms: (β = −0.27; 95% CI, −0.47 to −0.08; P = .005). Probing the interaction with simple slopes at ±SD revealed that for the control group, racial discrimination was significantly associated with depressive symptoms (β = 0.39; 95% CI, 0.23 to 0.54; P &amp;amp;lt; .001), while for the SAAF group, there was no association between racial discrimination and depressive symptoms (β = 0.12; P = .09). Conclusions and Relevance This randomized clinical trial found that the SAAF intervention reduced the incidence of racism-associated mental health symptoms among Black adolescents. SAAF is recommended for dissemination to health care practitioners working with rural Black adolescents. Trial Registration ClinicalTrials.gov Identifier: NCT03590132
Genetic Liability to Posttraumatic Stress Disorder Symptoms and Its Association With Cardiometabolic and Respiratory Outcomes
Authors: Gita A. Pathak, Kritika Singh, Karmel W. Choi, Yu Fang, Manuela R. Kouakou, Younga Heather Lee, Xiang Zhou, Lars G. Fritsche, Frank R. Wendt, Lea K. Davis, Renato Polimanti
Journal: JAMA Psychiatry (2023)

Posttraumatic stress disorder (PTSD) has been reported to be a risk factor for several physical and somatic symptoms. However, the genetics of PTSD and its potential association with medical outcomes remain unclear.
Prevalence, Awareness, and Treatment of Elevated LDL Cholesterol in US Adults, 1999-2020
Authors: Ahmed Sayed, Ann Marie Navar, Leandro Slipczuk, Christie M. Ballantyne, Zainab Samad, Carl J. Lavie, Salim S. Virani
Journal: JAMA Cardiology (2023)

This cross-sectional study compares the prevalence, awareness, and treatment of elevated low-density lipoprotein (LDL) cholesterol in US adults in 1999-2000 vs 2017-2020.
Amputation Rates and Associated Social Determinants of Health in the Most Populous US Counties
Authors: Daniel Kassavin, Lucas Mota, Claire A. Ostertag-Hill, Monica Kassavin, David U. Himmelstein, Steffie Woolhandler, Sophie X. Wang, Patric Liang, Marc L. Schermerhorn, Sivamainthan Vithiananthan, Moon Kwoun
Journal: JAMA Surgery (2023)

Social Determinants of Health (SDOH) have been found to be associated with health outcome disparities in patients with peripheral artery disease (PAD). However, the association of specific components of SDOH and amputation has not been well described.
Pulsed Field Closes Gender Gap in Atrial Fibrillation Ablation—Electrifying Insights
Authors: Peter M. Kistler, Louise Segan
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Nontraumatic Amputations in the United States—An Urgent Matter of Equity
Authors: Steve Singh Gill, Mihir Chaudhary, Tanya L. Zakrison
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Long COVID Linked With Viral Persistence, Serotonin Decline
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal